The synthesis and comparative receptor binding affinities of novel, isomeric pyridoindolobenzazepine scaffolds

Raghavan Rajagopalan; Acintya Bandyopadhyaya; Desikan R Rajagopalan; Parthasarathi Rajagopalan

doi:10.1016/j.bmcl.2013.12.024

The synthesis and comparative receptor binding affinities of novel, isomeric pyridoindolobenzazepine scaffolds

Bioorg Med Chem Lett. 2014 Jan 15;24(2):576-9. doi: 10.1016/j.bmcl.2013.12.024. Epub 2013 Dec 11.

Authors

Raghavan Rajagopalan¹, Acintya Bandyopadhyaya¹, Desikan R Rajagopalan¹, Parthasarathi Rajagopalan²

Affiliations

¹ Daya Drug Discoveries, Inc., University of Missouri, St. Louis, One University Blvd., St. Louis, MO 63303, USA.
² Daya Drug Discoveries, Inc., University of Missouri, St. Louis, One University Blvd., St. Louis, MO 63303, USA. Electronic address: ramajayam30@yahoo.com.

PMID: 24365159
DOI: 10.1016/j.bmcl.2013.12.024

Abstract

Compounds 7, 8, and 9, derived from the novel scaffolds 3, 5, and 6, were synthesized and evaluated in vitro. The b,c→c,d shift of the E-phenyl ring resulted in a large decrease (ca. 20- to 1000-fold) in binding to the 5-HT2A, 5-HT2C and H2, receptors, and a modest decrease (ca. 10- to 20-fold) in binding to the 5-HT5A, D2, D5, and α1D, receptors. The b,c→d,e shift resulted in a large decrease in binding to the 5-HT1D, 5-HT2C, 5-HT6, and H1 receptors, a modest decrease in binding to 5-HT1A, 5-HT5A and D2, D5, α2B, and H2 receptors, and a large increase in affinity to the 5-HT3, 5-HT6, and σ1 receptors.

Keywords: Dopamine; Gamma carboline; Histamine; Pyridoindolobenzazepine; Serotonin.

Publication types

Comparative Study
Research Support, N.I.H., Extramural

MeSH terms

Benzodiazepinones / chemistry*
Benzodiazepinones / metabolism*
Isomerism
Protein Binding / physiology
Protein Structure, Tertiary
Receptors, Cell Surface / chemistry*
Receptors, Cell Surface / metabolism*

Substances

Benzodiazepinones
Receptors, Cell Surface
propizepine